Variation of muscarinic activities of oxotremorine analogues

Abstract

AbstractClose analogues of oxotremorine (a potent muscarinic agonist with marked CNS actions) were examined for inhibition of ligand binding in rat cortex membranes using 3H‐oxotremorine‐M and 3H‐quinuclidinyl benzilate, and in simple tests in vivo for autonomic and behavioural effects (induction of salivation, hypothermia, tremor, inhibition of locomotion in mice; inhibition of sparring and rearing behaviours in rats). The combined use of these tests indicated whether compounds were agonists, antagonists, or inactive at muscarinic receptors, and gave preliminary details of their pharmacological profile and selectivity on different muscarinic responses. The analogue known as BM5 was a partial agonist with a selective profile. It was considered of interest for further study as a possible candidate for therapeutic use in the memory impairment (and acetylcholine deficit) of Alzheimer's disease. In studies in tests for long‐term (24‐hr passive avoidance) and short‐term, working (5‐min arena maze) memory/cognition in rats, no evidence of enhancement was obtained with BM5.